This application claims Paris Convention priority of DE 101 38 961.2-33 filed on Aug. 8, 2001, the entire disclosure of which is hereby incorporated by reference.
The invention concerns a nuclear magnetic resonance (NMR) method for spatially resolved measurement of the distribution of NMR signals of metabolites (CSI) with low signal intensity, wherein a sequence of radio frequency (RE) pulses, which are mutually offset at a time interval of a repetition time TR, is applied to a spin ensemble and magnetic gradient fields are switched, of which at least one causing encoding of the excited spins.
A method of this type is known e.g. from the publication by T. R. Brown et al. xe2x80x9cNMR chemical shift imaging in three dimensionsxe2x80x9d, Proc. Natl. Avad. Sci. USA, Vol. 79, 3523-3526 (1982).
To measure the spatial distribution of metabolites, one uses today conventionally the so-called chemical shift imaging (CSI) method wherein a signal is recorded through repeating an excitation with the corresponding excitation pulses which can be carried out with spatial selectivity for selecting a partial volume. The excitation steps are thereby repeated at a time interval TR, wherein TR is within the magnitude of the longitudinal relaxation time T1 of the observed metabolites to avoid signal saturation. The recording is thereby often very inefficient since the signal decays with the decay constant T2*, wherein T2* is much smaller than TR due to magnetic field inhomogeneities such that the actual useful time of data recording is very small compared to TR.
The method of steady-state free precession (SSFP) (Carr H Y, Phys. Rev. 112, 1693 (1958) presented by Carr in 1958 has much more efficient signal recording in comparison therewith. Therein, application of a regular sequence of radio frequency pulses produces steady state magnetization which is read out in the time interval between the pulses. The magnetization strength depends on the resonance frequency of the observed spins. In the preferred implementation, the phase of subsequent pulses is alternated. For spins, which experience dephasing by 180xc2x0 in the time interval TR between two pulses, the signal is thereby minimized.
For MR imaging (i.e. measurement of the proton density), this so-called trueFISP method (also called balanced FFE or FIESTA) has already been established (Oppelt A et al, electromedica 54, 15 (1986) and is often used with new devices since the available rapid gradient systems can achieve repetition times of typically TR less than 5 ms which are short enough to prevent image artefacts which are produced by the signal cancellation of spins which are dephased by field inhomogeneities.
There are approaches of optimizing the behavior of magnetization in the transition phase from the balanced state into the steady state. Initialization with a pulse with half a flip angle is introduced here which precedes the following sequence at a time interval of preferably TR/2 (Deimling M, Heid O. Magnetization prepared true FISP imaging. In: Proceedings of the 2nd Annual Meeting of the Society of Magnetic Resonance, San Francisco, 1994, p. 495). Also more recent solutions with other preparation phases are known.
For applications in proton imaging, trueFISP is therefore established as method for very effective data recording. Applications for localized spectroscopy with SSFP methods and for measuring the spatial distribution of metabolites were not yet reported although the small efficiency of data recording of conventional methods and the associated long measuring times are the main problem of in vivo MR spectroscopy.
The reason therefore is the fact that the SSFP signal mechanism primarily and obviously eliminates spectroscopic information since spins are refocused independent of their resonance frequency and therefore give a non-distinguishable contribution to the entire signal and the differentiation of spins of different chemical shifts (and therefore different resonance frequencies) desired in spectroscopy is lost.
In contrast thereto, it is the underlying purpose of the present invention to improve a method of the above-mentioned type such that the above-discussed disadvantages can be eliminated. The invention is to present in particular a new method with the aim that the advantages of SSFP methods can still be used for spectroscopic recordings and in particular for chemical shift imaging.
This object is achieved in accordance with the invention in an effective fashion in that the repetition time TR between the exciting RF pulses is selected to be in the magnitude of the transverse relaxation time T2* of the spins to be excited at the most and that the magnetic gradient fields are selected such that their action integral over a repetition time of a length of TR is zero such that NMR signals are produced according to the principle of steady state free precession (SSFP).
A drastically reduced repetition time TR compared to conventional CSI recordings and switching of integrally completely balanced gradients permits maintenance of the spectroscopic information of chemical shift also for SSFP recordings. This permits utilization of the advantages of SSFP methods also for spectroscopy.
One variant of the inventive method is particularly preferred wherein the repetition time TR is selected to be between 1 and 100 ms, preferably between 5 and 20 ms. The optimum chosen repetition time Tr depends on the other experimental parameters. The above-mentioned values are valid in particular for application of a homogeneous NMR magnetic field B in the magnitude of 1-2 tesla.
The signal recording time TAQ is usually always smaller than the repetition time TR. The signal-to-noise ratio per time unit is particularly large when the signal recording time TAQ is selected to be slightly smaller than TR, preferably TAQxe2x89xa60.95 TR.
In a further development of this method variant, the signal acquisition is always carried out when no RF pulses are currently irradiated. In this fashion, the NMR signal can be optimized with respect to noise minimization.
In a particularly preferred variant of the inventive method, RF pulses are irradiated and temporally variable magnetic gradient fields are selected for spatial encoding according to the principle of the spatially resolved Fourier transformation method. This greatly facilitates reconstruction of spatially resolved images of the metabolites from the recorded NMR signals.
In a further preferred method variant, switching of a magnetic gradient field spatially limits the excitation volume simultaneously with irradiation of the exciting RF pulses. This facilitates precise limitation of the NMR measurement to certain parts of the measuring object thereby keeping disturbances and noise outside of the zone of interest away from the signals.
A further development of this method variant is characterized in that the direction and amplitude of the slice selection gradient is varied from one recording step to the next, thereby further limiting the measuring volume to the region in which the SSFP condition is met. This limits the interesting measuring volume in several dimensions to permit precise selection of very special subvolumes in the measuring object.
In a further particularly preferred variant of the inventive method, the NMR recording is repeated several times thereby varying the measuring frequency such that the signal intensities of several NMR signals of different resonance frequencies overlap in a characteristic fashion across the measured signal intensity as a function of the measuring frequency.
As an alternative or supplement, a further method variant provides that the NMR recording is repeated several times thereby varying a phase increment between subsequent RF pulses such that the signal intensities of several NMR signals of different resonance frequencies overlap in a characteristic fashion across the measured signal intensity as function of the phase increment between subsequent RF pulses.
In both method variants (and combinations thereof) the signal intensities associated with the individual resonances can be determined by calculating methods known per se.
In a further advantageous variant of the inventive method, RF pulses with alternating flip angle xcex1 or phase increments of 180xc2x0 are selected. Usually, the highest possible signal intensities can be achieved.
One variant of the inventive method is also advantageous wherein RF pulses with a flip angle xcex1 are selected such that cos xcex1=(T1/T2xe2x88x921)/(T1/T2+1) wherein T1 is the longitudinal relaxation time and T2 is the transverse relaxation time without taking into consideration the susceptibility effects. For metabolites wherein T1 and T2 is known, the NMR signal can be maximized.
Further advantages of the invention can be extracted from the description and the drawing. The features mentioned above and below can be used in accordance with the invention either individually or collectively in any arbitrary combination. The embodiments shown and described are not to be understood as exhaustive enumeration but rather have exemplary character for describing the invention.
The invention is shown in the drawing and explained in more detail by means of embodiments.